Our collective evidence gathered during this research project indicates that the connectivity and ultrastructure of the visual system of the mutant anophthalmic mouse resembles closely that of the normal mouse by many parameters. This varied evidence has been derived from (1) in situ microscopic analysis of the dorsal lateral geniculate (LGd) neuronal and neuroglial populations and the dendritic differentiation of the layer V pyramidal neurons in the striate cortex; (2) axoplasmic tracer studies in normal, normalenucleated, and anophthalmic mice ; (3) morphologic analysis of the oculomotor nuclei; and (4) cortical ablation studies. The existence of apparent normal connectivity in the visual system in the anophthalmic mouse, despite the total absence of visual stimuli, suggests that other kinds of input maintain these visual centers and that this mutant mouse may be a valid model for determining the non-visual input into the visual pathways. During the -07 year strong emphasis will be placed on analysis of the differentiation of the visual system. The embryonic development of the visual system in normal and anophthalmic mice will be compared by serial section analysis and transmission electron microscopy. Intrauterine surgery will be performed to enucleate by cauterization normal embryonic mice with pigmented eyes to provide an exprimental "control" preparation for comparison with anophthalmic and intact control mice. Also via intrauterine manipulation, the eyes of control embryonic mice will be injected with radioactive amino acids to time the establishment of connectivity in the mouse visual system by autoradiography. A major difference in the LGd of normal and anophthalmic adult mice is the presence of distinctive large terminals in the anophthalmia which replace the retinal afferents. This synaptic association will be studied by the freeze fracture procedure. The C14-deoxyglucose method will be introduced into our investigation in order to identify possible differences in neuronal metabolism in relation to physiologic stimulation.